tbuckley/cabot-search huggingface dataset:
Frequency, Penetrance, and Variable Expressivity of Dilated Cardiomyopathy–Associated Putative Pathogenic Gene Variants in UK Biobank Participants
Authors: Ravi A. Shah, Babken Asatryan, Ghaith Sharaf Dabbagh, Nay Aung, Mohammed Y. Khanji, Luis R. Lopes, Stefan van Duijvenboden, Anthony Holmes, Daniele Muser, Andrew P. Landstrom, Aaron Mark Lee, Pankaj Arora, Christopher Semsarian, Virend K. Somers, Anjali T. Owens, Patricia B. Munroe, Steffen E. Petersen, C. Anwar A. Chahal
Journal: Circulation (2022)

Background: There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional, and arrhythmic disease features. Methods: UK Biobank participants who had undergone whole exome sequencing, ECG, and cardiovascular magnetic resonance imaging were selected for study. Three variant-calling strategies (1 primary and 2 secondary) were used to identify participants with putative pathogenic variants in 44 DCM genes. The observed phenotype was graded DCM (clinical or cardiovascular magnetic resonance diagnosis); early DCM features, including arrhythmia or conduction disease, isolated ventricular dilation, and hypokinetic nondilated cardiomyopathy; or phenotype-negative. Results: Among 18 665 individuals included in the study, 1463 (7.8%) possessed ≥1 putative pathogenic variant in 44 DCM genes by the main variant calling strategy. A clinical diagnosis of DCM was present in 0.34% and early DCM features in 5.7% of individuals with putative pathogenic variants. ECG and cardiovascular magnetic resonance analysis revealed evidence of subclinical DCM in an additional 1.6% and early DCM features in an additional 15.9% of individuals with putative pathogenic variants. Arrhythmias or conduction disease (15.2%) were the most common early DCM features, followed by hypokinetic nondilated cardiomyopathy (4%). The combined clinical/subclinical penetrance was ≤30% with all 3 variant filtering strategies. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive/strong evidence genes as compared with those with variants in moderate/limited evidence genes. Conclusions: In the UK Biobank, ≈1 of 6 of adults with putative pathogenic variants in DCM genes exhibited early DCM features potentially associated with DCM genotype, most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation or dysfunction.
Prognosis of Patients With Primary Melanoma Stage I and II According to American Joint Committee on Cancer Version 8 Validated in Two Independent Cohorts: Implications for Adjuvant Treatment
Authors: Claus Garbe, Ulrike Keim, Teresa Amaral, Carola Berking, Thomas K. Eigentler, Lukas Flatz, Anja Gesierich, Ulrike Leiter, Rudolf Stadler, Cord Sunderkötter, Thomas Tüting, Jochen Utikal, Uwe Wollina, Lisa Zimmer, Christos C. Zouboulis, Paolo A. Ascierto, Alexander M.M. Eggermont, Jean-Jacques Grob, Axel Hauschild, Lidija Kandolf Sekulovic, Georgina V. Long, Jason J. Luke, Olivier Michielin, Ketty Peris, Dirk Schadendorf, John M. Kirkwood, Paul C. Lorigan
Journal: Journal of Clinical Oncology (2022)

The first randomized trial of adjuvant treatment with checkpoint inhibitor in stage II melanoma reported a significant reduction in risk of tumor recurrence. This study evaluates two independent data sets to further document survival probabilities for patients with primary stage I and II melanoma.The Central Malignant Melanoma Registry (CMMR) in Germany evaluated 17,544 patients with a primary diagnosis of stage I and II melanoma from 2000 to 2015. The exploratory cohort consisted of 6,725 patients from the Center for Dermato-Oncology at the University of Tübingen, and the confirmatory cohort consisted of 10,819 patients from 11 other German centers. Survival outcomes were compared with published American Joint Committee on Cancer version 8 (AJCCv8) stage I and II survival data.For the two CMMR cohorts in stage IA compared with the AJCCv8 cohort, melanoma-specific survival rates at 10 years were 95.1%-95.6% versus 98%; 89.7%-90.9% versus 94% in stage IB; 80.7%-83.1% versus 88% in stage IIA; 72.0%-79.9% versus 82% in stage IIB; and 57.6%-64.7% versus 75% in stage IIC, respectively. Recurrence rates were approximately twice as high as melanoma-specific mortality rates in stages IA-IIA.The melanoma-specific survival rates in the two CMMR cohorts across stages I and II are less favorable than published in AJCCv8. This has important implications for the consideration of adjuvant treatment in this population.
Effectiveness of exercise via telehealth for chronic disease: a systematic review and meta-analysis of exercise interventions delivered via videoconferencing
Authors: Riley CC Brown, Jeff S Coombes, Klaus Jungbluth Rodriguez, Ingrid J Hickman, Shelley E Keating
Journal: British Journal of Sports Medicine (2022)

Objective To investigate the effectiveness of videoconferencing exercise interventions for people with chronic diseases. Design Systematic review incorporating meta-analysis. Data sources PubMed, Cinahl, MEDLINE, Web of Science, Embase and Scopus. Eligibility criteria The current literature was searched following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Trials analysing participants with chronic disease undergoing aerobic and/or resistance exercise training over videoconferencing, with exercise capacity and/or quality of life outcomes were included. Meta-analyses were conducted for between-group comparisons of exercise capacity and quality of life. Risk of bias was analysed using the Downs and Black quality checklist and the certainty of evidence with Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results Thirty-two trials were included in this review, of which 12 were comparator trials. Small–moderate between-group (videoconferencing vs comparator) effects favouring videoconferencing were seen for studies using a non-exercising comparator for exercise capacity (standardised mean difference (SMD)=0.616, 95% CI 0.278 to 0.954; p=&lt;0.001) and quality of life (SMD=0.400, 95% CI 0.099 to 0.701; p=0.009). Small effects favouring videoconferencing were observed for studies using an exercising comparator for quality of life (SMD=0.271, 95% CI 0.028 to 0.515; p=0.029) and exercise capacity (SMD=0.242, 95% CI 0.059 to 0.426; p=0.009). Moderate risk of bias was identified for included studies (16.3±3.6/28), with GRADE certainty ratings of ‘low’ (quality of life) and ‘moderate’ (exercise capacity). Session attendance was 70% and was reported in 23 trials. No serious adverse events relating to videoconferencing were found. Nine trials documented the total number of technical issues that occurred in 17% of the sessions. Positive satisfaction outcomes were associated with ease of access and usefulness of technology. Conclusion In patients with chronic disease, videoconferencing exercise interventions appear to be feasible and effective for improving exercise capacity and quality of life. More robust methodology is needed in future studies to improve the certainty of the evidence. PROSPERO registration number CRD42020191243.
Guided, internet based, cognitive behavioural therapy for post-traumatic stress disorder: pragmatic, multicentre, randomised controlled non-inferiority trial (RAPID)
Authors: Jonathan I Bisson, Cono Ariti, Katherine Cullen, Neil Kitchiner, Catrin Lewis, Neil P Roberts, Natalie Simon, Kim Smallman, Katy Addison, Vicky Bell, Lucy Brookes-Howell, Sarah Cosgrove, Anke Ehlers, Deborah Fitzsimmons, Paula Foscarini-Craggs, Shaun R S Harris, Mark Kelson, Karina Lovell, Maureen McKenna, Rachel McNamara, Claire Nollett, Tim Pickles, Rhys Williams-Thomas
Journal: BMJ (2022)

To determine if guided internet based cognitive behavioural therapy with a trauma focus (CBT-TF) is non-inferior to individual face-to-face CBT-TF for mild to moderate post-traumatic stress disorder (PTSD) to one traumatic event.
Impact of exercise intervention-based changes on physical function biomarkers in older adults after hospital discharge: A systematic review with meta-analysis of randomized clinical trials
Authors: Marcelo A.S. Carneiro, Gersiel Oliveira-Júnior, Pâmela Castro-e-Souza, Anselmo A. Oliveira, Paulo R.P. Nunes, Mikel Izquierdo, Eduardo L. Cadore, Edilson S. Cyrino
Journal: Ageing Research Reviews (2022)
NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 3.2022
Authors: William G. Wierda, Jennifer Brown, Jeremy S. Abramson, Farrukh Awan, Syed F. Bilgrami, Greg Bociek, Danielle Brander, Asher A. Chanan-Khan, Steve E. Coutre, Randall S. Davis, Herbert Eradat, Christopher D. Fletcher, Sameh Gaballa, Armin Ghobadi, Muhammad Saad Hamid, Francisco Hernandez-Ilizaliturri, Brian Hill, Paul Kaesberg, Manali Kamdar, Lawrence D. Kaplan, Nadia Khan, Thomas J. Kipps, Shuo Ma, Anthony Mato, Claudio Mosse, Stephen Schuster, Tanya Siddiqi, Deborah M. Stephens, Chaitra Ujjani, Nina Wagner-Johnston, Jennifer A. Woyach, J. Christine Ye, Mary A. Dwyer, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2022)

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.
Mental health outcomes of male UK military personnel deployed to Afghanistan and the role of combat injury: analysis of baseline data from the ADVANCE cohort study
Authors: Daniel Dyball, Alexander N Bennett, Susie Schofield, Paul Cullinan, Christopher J Boos, Anthony M J Bull, Simon Wessely, Sharon A M Stevelink, Nicola T Fear
Journal: The Lancet Psychiatry (2022)

BackgroundThe long-term psychosocial outcomes of UK armed forces personnel who sustained serious combat injuries during deployment to Afghanistan are largely unknown. We aimed to assess rates of probable post-traumatic stress disorder (PTSD), depression, anxiety, and mental health-associated multimorbidity in a representative sample of serving and ex-serving UK military personnel with combat injuries, compared with rates in a matched sample of uninjured personnel.MethodsThis analysis used baseline data from the ADVANCE cohort study, in which injured individuals were recruited from a sample of UK armed forces personnel who were deployed to Afghanistan and had physical combat injuries, according to records provided by the UK Ministry of Defence. Participants from the uninjured group were frequency-matched by age, rank, regiment, deployment, and role on deployment. Participants were recruited through postal, email, and telephone invitations. Participants completed a comprehensive health assessment, including physical health assessment and self-reported mental health measures (PTSD Checklist, Patient Health Questionnaire-9, and Generalised Anxiety Disorder-7). The mental health outcomes were rates of PTSD, depression, anxiety, and mental health-associated multimorbidity in the injured and uninjured groups. The ADVANCE study is ongoing and is registered with the ISRCTN registry, ISRCTN57285353.Findings579 combat-injured participants (161 with amputation injuries and 418 with non-amputation injuries) and 565 uninjured participants were included in the analysis. Participants had a median age of 33 years (IQR 30–37 years) at the time of assessment. 90·3% identified as White and 9·7% were from all other ethnic groups. The rates of PTSD (16·9% [n=89] vs 10·5% [n=53]; adjusted odds ratio [AOR] 1·67 [95% CI 1·16–2·41], depression (23·6% [n=129] vs 16·8% [n=87]; AOR 1·46 [1·08–2·03]), anxiety (20·8% [n=111] vs 13·5% [n=71]; AOR 1·56 [1·13–2·24]) and mental health-associated multimorbidity (15·3% [n=81] vs 9·8% [n=49]; AOR 1·62 [1·12–2·49]) were greater in the injured group than the uninjured group. Minimal differences in odds of reporting any poor mental health outcome were noted between the amputation injury subgroup and the uninjured group (AOR range 0·77–0·97), whereas up to double the odds were noted for the non-amputation injury subgroup compared with the uninjured group (AOR range 1·74–2·02).InterpretationSerious physical combat injuries were associated with poor mental health outcomes. However, the type of injury sustained influenced this relationship. Regardless of injury, this cohort represents a group who present with greater rates of PTSD than the general population, as well as increased psychological burden from multimorbidity.FundingThe ADVANCE Charity.
Proteogenomic, Epigenetic, and Clinical Implications of Recurrent Aberrant Splice Variants in Clear Cell Renal Cell Carcinoma
Authors: Andrew Chang, Nicholas H. Chakiryan, Dongliang Du, Paul A. Stewart, Yonghong Zhang, Yijun Tian, Alex C. Soupir, Kiah Bowers, Bin Fang, Ashley Morganti, Jamie K. Teer, Youngchul Kim, Philippe E. Spiess, Jad Chahoud, Jerald D. Noble, Ryan M. Putney, Anders E. Berglund, Timothy J. Robinson, John M. Koomen, Liang Wang, Brandon J. Manley
Journal: European Urology (2022)
The enduring gap in educational attainment in schizophrenia according to the past 50 years of published research: a systematic review and meta-analysis
Authors: Nicolás A Crossley, Luz María Alliende, Leticia S Czepielewski, David Aceituno, Carmen Paz Castañeda, Camila Diaz, Barbara Iruretagoyena, Carlos Mena, Cristian Mena, Juan Pablo Ramirez-Mahaluf, Angeles Tepper, Javiera Vasquez, Lais Fonseca, Viviane Machado, Camilo E Hernández, Cristian Vargas-Upegui, Gladys Gomez-Cruz, Luis F Kobayashi-Romero, Tomas Moncada-Habib, Celso Arango, Deanna M Barch, Cameron Carter, Christoph U Correll, Nelson B Freimer, Philip McGuire, Sara Evans-Lacko, Eduardo Undurraga, Rodrigo Bressan, Clarissa S Gama, Carlos Lopez-Jaramillo, Camilo de la Fuente-Sandoval, Alfonso Gonzalez-Valderrama, Juan Undurraga, Ary Gadelha
Journal: The Lancet Psychiatry (2022)
Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology
Authors: William J. Gradishar, Meena S. Moran, Jame Abraham, Rebecca Aft, Doreen Agnese, Kimberly H. Allison, Bethany Anderson, Harold J. Burstein, Helen Chew, Chau Dang, Anthony D. Elias, Sharon H. Giordano, Matthew P. Goetz, Lori J. Goldstein, Sara A. Hurvitz, Steven J. Isakoff, Rachel C. Jankowitz, Sara H. Javid, Jairam Krishnamurthy, Marilyn Leitch, Janice Lyons, Joanne Mortimer, Sameer A. Patel, Lori J. Pierce, Laura H. Rosenberger, Hope S. Rugo, Amy Sitapati, Karen Lisa Smith, Mary Lou Smith, Hatem Soliman, Erica M. Stringer-Reasor, Melinda L. Telli, John H. Ward, Kari B. Wisinski, Jessica S. Young, Jennifer Burns, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2022)

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org .
Comparison of infection‐induced and vaccine‐induced immunity against COVID‐19 in patients with cirrhosis
Authors: Binu V. John, Akash Doshi, Raphaella D. Ferreira, Tamar H. Taddei, David E. Kaplan, Seth A. Spector, Yangyang Deng, Dustin Bastaich, Bassam Dahman
Journal: Hepatology (2022)

Background and Aims: Immunity to SARS‐CoV‐2 can be infection or vaccine‐induced. Cirrhosis is associated with vaccine hyporesponsiveness, but whether there is decreased immunity after SARS‐CoV‐2 infection in unvaccinated patients with cirrhosis is unknown. The objective of our study was to compare infection‐induced and vaccine‐induced immunity against COVID‐19 among patients with cirrhosis. Methods: This was a retrospective cohort study among US Veterans with cirrhosis between November 27, 2020, and November 16, 2021, comparing a vaccine‐induced immunity group, defined as participants without a documented SARS‐CoV‐2 infection but fully vaccinated with two doses of an mRNA vaccine, and infection‐associated immunity group, defined as unvaccinated participants who had a positive SARS‐CoV‐2 polymerase chain reaction (PCR). Both groups were propensity score matched for observed characteristics, including location, and the date of the immunity acquiring event, to control for the community prevalence of COVID‐19 variants. The outcome was a positive SARS‐CoV‐2 PCR more than 60 days after previous infection in the infection‐induced, or after full vaccination in the vaccine‐induced immunity group. Results: We compared 634 participants in the infection‐induced immunity group with 27,131 participants in the vaccine‐induced immunity group using inverse propensity of treatment weighting. Vaccine‐induced immunity was associated with a reduced odds of developing SARS‐CoV‐2 infection (adjusted hazard ratio [aHR], 0.18; 95% confidence interval [CI], 0.16–0.20, p &lt; 0.0001). On multivariable logistic regression, vaccine‐induced immunity was associated with reduced odds of developing symptomatic (adjusted odds ratio [aOR], 0.36; 95% CI, 0.33–0.41, p &lt; 0.0001), moderate/severe/critical (aOR, 0.27; 95% CI, 0.22–0.31, p &lt; 0.0001), and severe or critical COVID‐19 (aOR, 0.20; 95% CI, 0.16–0.26, p &lt; 0.001), compared with infection‐induced immunity. Conclusions: In participants with cirrhosis, vaccine‐induced immunity is associated with reduced risk of developing COVID‐19, compared with infection‐induced immunity.
Retraction Note to: LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis
Authors: Yiran Liang, Xiaojin Song, Yaming Li, Bing Chen, Wenjing Zhao, Lijuan Wang, Hanwen Zhang, Ying Liu, Dianwen Han, Ning Zhang, Tingting Ma, Yajie Wang, Fangzhou Ye, Dan Luo, Xiaoyan Li, Qifeng Yang
Journal: Molecular Cancer (2022)

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-020-01206-5
The Evolving Role of Neoadjuvant Therapy for Operable Breast Cancer
Authors: Laura M. Spring, Yael Bar, Steven J. Isakoff
Journal: Journal of the National Comprehensive Cancer Network (2022)

The role of neoadjuvant therapy (NAT) for localized breast cancer has evolved tremendously over the past several years. Currently, NAT is the preferred option for high-risk early triple-negative (TN) and HER2-positive (HER2+) breast cancers and is indicated for some estrogen receptor–positive (ER+) breast cancers. In addition to traditional absolute indications for NAT, relative indications such as the assessment of outcomes at the time of surgery and guidance of treatment escalation and de-escalation have greatly evolved in recent years. Pathologic complete response (pCR) and the Residual Cancer Burden (RCB) index are highly prognostic for disease recurrence and survival, mainly in patients with TN or HER2+ disease. Furthermore, post-NAT escalation strategies have been shown to improve long-term outcomes of patients who do not achieve pCR. Additionally, by allowing the direct assessment of drug effect on the tumor, the neoadjuvant setting has become an attractive setting for the exploration of novel agents and the identification of predictive biomarkers. Neoadjuvant trial design has also evolved, using adaptive treatment approaches that enable treatment de-escalation or escalation based on response. However, despite multiple practice-changing neoadjuvant trials and the addition of various new agents to the neoadjuvant setting for early breast cancer, many key questions remain. For example, patient selection for neoadjuvant immunotherapy in TN breast cancer, de-escalation methods in HER2+ breast cancer, and the use of gene expression profiles to guide NAT recommendations in ER+ breast cancer. This article reviews the current approach for NAT in localized breast cancer as well as evolving NAT strategies, the key remaining challenges, and the ongoing work in the field.
Covid-19: Long covid risk is lower with omicron than delta, researchers find
Authors: Jacqui Wise
Journal: BMJ (2022)

Covid-19: Long covid risk is lower with omicron than delta, researchers find Jacqui WiseThe risk of developing long covid is lower among people with the omicron variant of SARS-CoV-2 than with delta, shows an analysis of self reported data to the UK ZOE covid app.
Tanycytes control hypothalamic liraglutide uptake and its anti-obesity actions
Authors: Monica Imbernon, Chiara Saponaro, Hans Christian Cederberg Helms, Manon Duquenne, Daniela Fernandois, Eleonora Deligia, Raphael G.P. Denis, Daniela Herrera Moro Chao, Sowmyalakshmi Rasika, Bart Staels, François Pattou, Frank W. Pfrieger, Birger Brodin, Serge Luquet, Caroline Bonner, Vincent Prevot
Journal: Cell Metabolism (2022)
Modern approaches to the calculation of ideal body weight and the association of its changes with digestive system diseases
Authors: Yu.M. Stepanov, L.V. Demeshkina, V.B. Yagmur, S.L. Melanich, R.M. Kislova
Journal: GASTROENTEROLOGY (2022)

Background. There has been growing interest in the relationship between body mass and digestive diseases. There is no consensus on the calculation of the ideal human weight and the effect of its changes on gastrointestinal diseases. Materials and methods. The Internet resources (PubMed, Scopus, Web of Science, Medline, and others) were analyzed for the period 1980–2020. Results. Various proposed formulas for diagnosing the ideal human weight are presented. The comparison of modern different methods to estimate body composition was done. The possibilities and benefits of using of bioelectrical impedance analysis were presented. The pros and cons of dual-energy x-ray absorptiometry (DEXA) for body composition assessment was described. The relationship between body mass and digestive diseases was presented. Overweight and obesity was shown to be associated with the development of diseases of the digestive system: functional disorders of the gastrointestinal tract, inflammatory bowel disease, gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, polyposis and colon cancer, hepatocellular carcinoma, gallstone disease, cholangiocarcinoma, pancreatic cancer, non-alcoholic fatty liver disease, and others. Conclusions. There are some associations between body mass and digestive diseases. Patient’s weight gain or loss may indirectly indicate the presence of gastrointestinal pathology, which must be taken into account by the clinician for diagnostic approach.